IgM-IgG mixed cryoglobulins occur in association with a distinct clinical syndrome of purpura, arthralgias and in about one-half cases, renal disease due to diffuse proliferative glomerulonephritis. A pathogenic role for these complexes is suggested by: a) systemic hypocomplementemia, and the ability of isolated cryoglobulins to activate complement in vitro, b) the presence of immune reactants (RF, HBsAg, AntiHBsAb) in isolated cryoproteins, and c) immunofluorescence studies showing deposition of specific immune reactants in vasculitis lesions or nephritis. A large number of these patients have subclinical liver disease or serological evidence of hepatitis B virus infection. The objective of the proposed research is to complete prior studies suggesting the presence of multiple circulating soluble and cryoprecipitable immune complexes in the sera of these patients, and to evaluate the diagnostic usefulness of the unlabeled enzyme (peroxidase-antiperoxidase, PAP) technique in the study of the pathological lesions of patients with this syndrome. Specifically, the presence of 7S IgM, low molecular weight (IgM, IgG) RF, antinuclear antibody activity in fractionated specimens, as well as HBsAg and anti Hb, Ab in certain cases, will be sought and correlated with the presence of immune complex-like material, determined by Clq binding activity. In cases where sufficient plasmapheresis material is available, we will isolate specific fractions by solid-phase immunoabsorption for the preparation of monospecific antisera. These antisera, as well as antisera to immunoglobulin class-specific, light chain, and complement components will be utilized for PAP studies, searching for specific antigenic determinants of circulating immune reactants in tissues. In select instances, immunofluorescence studies and direct elution will be utilized to corroborate data.